Effect of estrogen on right ventricular remodeling of monocrotaline-induced pulmonary arterial hypertension in rats and its mechanism.

OBJECTIVE: To elucidate the effect of estrogen on right ventricular remodeling of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats and its underlying mechanism. MATERIALS AND METHODS: Male Sprague- Dawley (SD) rats were adaptively fed for one week, and then, randomly divided into control group, MCT group, MCT+17-β estradiol (50 mg·kg-1·d-1) group, and MCT+17-β estradiol (100 mg·kg-1·d-1) group, with 8 rats in each group. PAH rat model was constructed by subcutaneous injection of 60 mg·kg-1 MCT for consecutive 4 weeks. The right external jugular vein was intubated to monitor rat RVSP (right ventricular systolic pressure) and mPAP (mean pulmonary arterial pressure). After animal procedures, RV (right ventricle) and LV+S (left ventricle+ventricular septum) of rat were harvested and weighed. Rat tibia was collected and recorded for its length, followed by calculation of RV/(LV+S) and RV/length of the tibia. HE staining and Masson staining were conducted to observe the pathological change and collagen deposition in RV, respectively. RV was prepared for homogenate, followed by detection of total antioxidant capacity (T-AOC) and malondialdehyde (MDA) activities. Expression levels of collagen I, collagen III, NOX4, and NF-κB in RV of PAH rats were detected by qRT-PCR and Western blot. RESULTS: Lower RVSP, mPAP, RV/(LV+S) and RV/length of the tibia were observed in rats of MCT+17-β estradiol (50 mg·kg-1·d-1) group and MCT+17-β estradiol (100 mg·kg-1·d-1) group compared with those of MCT group. Injection of 17-β estradiol (50 mg·kg-1·d-1 and 100 mg·kg-1·d-1) in PAH rats remarkably alleviated pathological changes and collagen deposition in RV. T-AOC activity increased, whereas MDA activity decreased in PAH rats injected with 17-β estradiol. Expression levels of collagen I, collagen III, NOX4, and NF-κB in RV of PAH rats were all downregulated by 17-β estradiol treatment. CONCLUSIONS: 17-β estradiol could remarkably alleviate MCT-induced right ventricular remodeling of PAH rats. It is suggested that 17-β estradiol exerts its protective role in PAH by inhibiting NOX4-mediated oxidative stress and NF-κB-mediated collagen deposition.